Immunotherapeutic Therapy

Immunotherapeutic Therapy

Immunotherapy, also known as biological therapy, involves activating or suppressing the immune system to combat disease.

Activation vs. Suppression Immunotherapies

  • Activation Immunotherapies: Designed to elicit or amplify an immune response, enhancing the body's natural defenses.

  • Suppression Immunotherapies: Focus on reducing or suppressing the immune response, crucial when the immune system is overactive.

Application in Veterinary Medicine

  • Primarily recognized in human medicine but increasingly applied in veterinary medicine.

  • Used for treating immune-mediated diseases in dogs, cats, and horses.

Immunosuppressive Agents

Glucocorticoids

  • Act as both anti-inflammatory and immunosuppressive drugs, impacting both innate and adaptive immune responses.

  • Bind to cytoplasmic glucocorticoid receptors (GCGRs), translocating to the cell nucleus to stimulate or inhibit gene transcription.

  • Results in reduced inflammation and pain relief.

  • Commonly used to treat allergic skin diseases and feline asthma.

  • Side effects can lead to blanket immunosuppression.

  • Mimic the effects of endogenous corticosteroids.

Cytotoxic Drugs

  • Target the cell cycle, used in treating autoimmune diseases in dogs.

  • Cell Cycle Phases:

    • M phase: Mitosis

    • G1 phase: RNA and protein synthesis

    • G0 phase: Resting state

    • S phase: DNA, RNA, and protein synthesis

  • Examples: Azathioprine and cyclophosphamide, often used with glucocorticoids for additive immunosuppressive effects.

  • Interfere with the cell cycle, providing steroid-sparing effects.

Cyclosporine

  • An anti-T cell medication originally for transplantation.

  • Used in treating allergies and inflammatory diseases in dogs.

  • Potential side effects: increased risk of infection, diarrhea, shedding, and possible liver and kidney damage.

Janus Kinase (JAK) Inhibitors

  • Block the JAK-STAT signaling pathway.

  • Inhibit cytokine production, key players in the inflammation process.

  • Mechanism:

    • Cytokines bind to cytokine receptors.

    • JAK kinases activate and phosphorylate transcription factors.

    • Transcription factors enter the nucleus, producing cytokines, creating an inflammation loop.

    • JAK inhibitors stop STAT phosphorylation, down-regulating inflammatory cytokine production.

  • Application: Treatment of canine allergic dermatitis.

Immunostimulatory Agents

  • Enhance the immune response.

  • Few licensed drugs available.

Plant or Microbial Extracts

  • Lethamenosol: Previously used but no longer recommended due to safety concerns.

  • Microbial extracts drive a strong Th1 immune response, important for fighting certain infections.

  • Parapox ovis: Associated with equine stress-related respiratory disease.

Allergen-Specific Immunotherapy (Hyposensitization)

  • Repeated injection of causative allergens.

  • Generates blocking antibodies and activates regulatory T cells (Tregs).

  • Beneficial for canine atopic dermatitis.

Intravenous Immunoglobulin Therapy

  • Uses purified human immunoglobulins.

  • Mechanism:

    • Binds to macrophage Fc receptor, modulating immune responses.

    • Blocks the interaction between Fas and Fas ligand, regulating cell death.

  • Useful for canine immune-mediated hemolytic anemia, thrombocytopenia, and autoimmune skin diseases.

Cytokine Therapy

  • Uses cytokines to modulate the immune response.

  • Example: Treatment of neutropenia in dogs using recombinant human cytokine G-CSF.

    • Stimulates bone marrow production of white blood cells.

    • Antibodies against the human version can block dog G-CSF function.

  • Can involve genetic material (mRNA, bacterial plasmid, or DNA-based precision) to enhance cytokine production.

Monoclonal Antibody Therapy

  • Designed to specifically block aspects of the immune response.

  • Inhibits antigen presentation, TCR T-cell activation, cytokine binding, and lymphocyte homing.

  • Potential side effect: Sensitization leading to adverse reactions.

Nexvet Innovation

  • Australian biotech company (later acquired by Zoetis).

  • Developed canine-specific antibody for blocking pain (based on a human antibody).

  • Successful treatment for pain in dogs, research extending to cats and horses.

Parasite Therapy

  • Based on the hygiene hypothesis: early exposure to germs and infections benefits immune system development.

  • Used to treat autoimmune diseases (e.g., irritable bowel syndrome in humans).

Pig Whipworm Model

  • Pig whipworm eggs ingested by humans, hatch and develop but are cleared after 14 days because humans are not their natural host.

  • Modulates immune response by:

    • Interacting with mucus in the stomach, changing the microbiome.

    • Decreasing bacterial attachment and diversity.

    • Promoting a type 2 T helper and Tregs response.

    • Direct secretion of anti-inflammatory molecules and promotion of barrier function by mucus production of globulin cells.

  • Potential for treating autoimmune diseases in cats and dogs.

Gene Therapy

  • Promising for monogenetic disorders (caused by a single gene mutation).

  • Corrects the underlying genetic defect and induces tolerance to specific proteins.

  • Being adopted in veterinary medicine, especially for dogs and horses.

Adjunct Immunotherapy

  • Complementary treatments such as acupuncture and herbal medicines.

  • Plant extracts and dietary supplements as potential adjuncts.

  • CBD from cannabis: Used to treat separation anxiety in pets.

Summary

  • Immunotherapy: Utilizes the body's immune system to fight diseases, particularly cancer and autoimmune diseases.

  • Immunosuppressive Agents: Glucocorticoids, cytotoxic drugs, and cyclosporine to dampen the immune response.

  • Immunostimulants: Enhance the immune response, useful in certain therapeutic contexts.

  • Adjunct Immunotherapy: Additional treatments that support the primary therapy, enhancing effectiveness.